Abstract
The recent International Society Urological Pathology (ISUP) Vancouver classification of renal neoplasia distinguishes between clear cell renal cell carcinoma (CCRCC) and multilocular cystic clear cell renal cell neoplasm of low malignant potential (mcCCRCNLMP). Current data supports the latter being a low aggressive neoplasm which does not recur or metastasize after definitive surgical treatment. Therefore, differentiating mcCCRCNLMP from low-grade CCRCC with cystic changes is important for patient management. The role of the pathologist is crucial in distinguishing between both entities. Since these tumors have overlapping molecular features, including 3p deletion and VHL mutations, it would be potentially clinically relevant to identify other molecular differences which might help to differentiate between these entities. We studied six different codons of KRAS and six codons of NRAS in mcCCRCNLMP and CCRCC of low grade and stage. All cases of CCRCC had a mutation in one of the studied KRAS codons. In contrast, no mutations were found in mcCCRCNLMP. We provide preliminary data to support that CCRCC and mcCCRCNLMP, in spite of their histologic similarity, show a different pattern of KRAS gene mutation, which is consistent with the observed differences in disease progression between these tumors.
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Srigley JR, Delahunt B, Eble JN, Egevard L, Epstein JI, Grignon D, Hes O, Moch H, Montironi R, Tickoo SK, Zhou M, Argani P (2013) The International Society of Urological Pathology (ISUP) Vancouver Classification of Renal Neoplasia. Am J Surg Pathol 37:1469–1489
Williamson SR, Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, Tan PH, Wang M, Zhang S, Maclennan GT, Baldridge LA, Cheng L (2012) Multilocular Cystic renal Cell Carcinoma: Similarities and Differences in Immunoprofile Compared with Clear Cell Renal Cell Carcinoma. Am J Surg Pathol 36:1425–1433
Williamson SR, MacLennan GT, Lopez-Beltran A, Montironi R, Tan PH, Martignoni G, Grignon DJ, Eble JN, Idrees MT, Scarpelli M, Cheng L (2013) Cystic partially regressed clear cell renal cell carcinoma: a potential mimic of multilocular cystic renal cell carcinoma. Histopathology 63:767–779
Mazzucchelli R, Scarpelli M, Montironi R, Cheng L, Lopez-Beltran A (2012) Multilocular cystic renal cell neoplasms of low malignant potential. Anal Quant Cytopathol Histopathol 34:235–258
Halat S, Eble JN, Grignon DJ, Lopez-Beltran A, Montironi R, Tan PH, Wang M, Zhang S, MacLennan GT, Cheng L (2010) Multilocular cystic renal cell carcinoma is a subtype of clear cell renal cell carcinoma. Mod Pathol 23:931–936
Mazzucchelli R, Galosi AB, Scarpelli M, Lopez-Beltran A, Cheng L, Montironi R (2014) Contemporary update on pathology-related issues of adult renal neoplasms. Anal Quant Cytopathol Histopathol 36:1–8
Shuch B, Amin A, Armstrong AJ, Eble JN, Ficarra V, Lopez-Beltran A, Martignoni G, Rini BI, Kutikov A (2015) Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity. Eur Urol 67:85–97
Lopez-Beltran A, Cheng L, Vidal A, Scarpelli M, Kirkali Z, Blanca A, Montironi R (2013) Pathology of renal cell carcinoma: an update. Anal Quant Cytopathol Histopathol 35:61–76
Kuroda N, Ohe C, Mikami S, Inoue K, Nagashima Y, Cohen RJ, Pan CC, Michal M, Hes O (2012) Multilocular cystic renal cell carcinoma with focus on clinical and pathobiological aspects. Histol Histopathol 27:969–974
Cheng L, Williamson SR, Zhang S, Maclennan GT, Montironi R, Lopez-Beltran A (2010) Understanding the molecular genetics of renal cell neoplasia: implications for diagnosis, prognosis and therapy. Expert Rev Anticancer Ther 10:843–864
Cheng L, Zhang S, MacLennan GT, Lopez-Beltran A, Montironi R (2009) Molecular and cytogenetic insights into the pathogenesis, classification, differential diagnosis, and prognosis of renal epithelial neoplasms. Hum Pathol 40:10–29
McGrath JP, Capon DJ, Smith DH, Chen EY, Seeburg PH, Goeddel DV, Levinson AD (1983) Structure and organization of the human Ki-ras proto-oncogene and a related processed pseudogene. Nature 304:501–506
Popescu NC, Amsbaugh SC, Di Paolo JA, Tronick SR, Aaronson SA, Swan DC (1985) Chromosomal localization of three human ras genes by in situ molecular hybridization. Somat Cell Mol Genet 11:149–155
Kranenburg O (2005) The KRAS oncogene: past, present, and future. Biochim Biophys Acta 1756:81–82
Delahunt B, Cheville JC, Martignoni G, Humphrey PA, Magi-Galluzzi C, McKenney J, Egevad L, Algaba F, Moch H, Grignon DJ, Montironi R, Srigley JR, Members of the ISUP Renal Tumor Panel (2013) The international society of urological pathology (ISUP) grading system for renal cell carcinoma and other prognostic parameters. Am J Surg Pathol 37:1490–1504
Trpkov K, Grignon DJ, Bonsib SM, Amin MB, Billis A, Lopez-Beltran A, Samaratunga H, Tamboli P, Delahunt B, Egevad L, Montironi R, Srigley JR, Members of the ISUP Renal Tumor Panel (2013) Handling and staging of renal cell carcinoma: the international society of urological pathology consensus (ISUP) conference recommendations. Am J Surg Pathol 37:1505–1517
Rozen S, Skaletsky H (2000) Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol 132:365–386
Bardelli A, Parsons DW, Silliman N, Ptak J, Szabo S, Saha S, Markowitz S, Willson JK, Parmigiani G, Kinzler KW, Vogelstein B, Velculescu VE (2003) Mutational analysis of the tyrosine kinome in colorectal cancers. Science 300:949
Montironi R, Mazzucchelli R, Scarpelli M, Lopez-Beltran A, Cheng L (2013) Update on selected renal cell tumors with clear cell features with emphasis on multilocular cystic clear cell renal cell carcinoma. Histol Histopath 28:1555–1566
Suzigan S, López-Beltrán A, Montironi R, Drut R, Romero A, Hayashi T, Gentili AL, Fonseca PS, deTorres I, Billis A, Japp LC, Bollito E, Algaba F, Requena-Tapias MJ (2006) Multilocular cystic renal cell carcinoma: a report of 45 cases of kidney tumor of low malignant potential. Am J Clin Pathol 125:217–222
Moch H (2010) Cystic renal tumors: new entities and novel concepts. Adv Anat Pathol 17:209–214
You D, Shim M, Jeong IG, Song C, Kim JK, Ro JY, Hong JH, Ahn H, Kim CS (2011) Multilocular cystic renal cell carcinoma: clinicopathological features and preoperative prediction using multiphase computer tomography. BJU Int 108:1444–1449
Von Teichman A, Comperat E, Behnke S, Storz M, Moch H, Schraml P (2011) VHL mutations and dysregulation pf pVHL- and PTEN-controlled pathways in multilocular cystic renal cell carcinoma. Mod Pathol 24:571–578
Yang L, Wu Q, Xu L, Zhang W, Zhu Y, Liu H, Xu J, Gu J (2015) Increased expression of colony stimulating factor-1 is a predictor of poor prognosis in patients with clear-cell renal cell carcinoma. BMC Cancer 15:67–78
Algaba F, Akaza H, Lopez-Beltran A, Martignoni G, Moch H, Montironi R, Reuter V (2011) Current pathology keys of renal cell carcinoma. Eur Urol 60:634–643
Stamatiou KN, Sofras F (2009) Multilocular cystic nephoma and multicystic clear cell carcinoma: two faces of the Roman god Janus? Int J Surg Pathol 17:170–171
Chen YN, Tickoo SK (2012) Spectrum of preneoplastic and neoplastic cystic lesions of the kidney. Arch Lab Pathol Med 136:400–409
Sinicrope FA, Shi Q, Smyrk TC, Thibodeau SN, Dienstmann R, Guinney J, Bot BM, Tejpar S, Delorenzi M, Goldberg RM, Mahoney M, Sargent DJ, Alberts SR (2015) Molecular markers identify subtypes of stage III colon cancer associated with patient outcomes. Gastroenterology 148:88–99
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Raspollini, M.R., Castiglione, F., Martignoni, G. et al. Unlike in clear cell renal cell carcinoma, KRAS is not mutated in multilocular cystic clear cell renal cell neoplasm of low potential. Virchows Arch 467, 687–693 (2015). https://doi.org/10.1007/s00428-015-1859-8
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DOI: https://doi.org/10.1007/s00428-015-1859-8